A gradient LC method for the determination of related substances in ritonavir (RTV) has been recently published in the International Pharmacopoeia. The method uses a base-deactivated reversed-phase C18 column kept at a temperature of 35 degrees C. The mobile phases consist of acetonitrile, phosphate buffer pH 4.0 and water. UV detection is performed at 240 nm. A system suitability test (SST) is described to govern the quality of the separation. Since no brand names of columns are mentioned in pharmacopoeial texts, analysts often have problems to select a suitable stationary phase which is only described in general terms. So, the separation towards RTV components was investigated on 18 C18 columns and correlation was made with the column classification system developed in our laboratory. The method was further evaluated using a Hypersil BDS C18 column (25 cm x 4.6mm i.d.), 5 microm, which was also used for the development of the method. A central composite design was applied to examine the robustness of the method. The method shows good precision, linearity, sensitivity and robustness. Four commercial samples were examined using this method.